Tumor tissue is densely packed with cancer cells, non‐cancerous cells, and ECM, forming functional structures. Cancer cells transfer extracellular vesicles (EVs) to modify surrounding normal cells into cancer‐promoting cells, establishing a tumor‐favorable environment together with other signaling molecules and structural components. Such tissue environments largely affect cancer cell properties, and so as EV‐mediated cellular communications within tumor tissue. However, current research on EVs focuses on functional analysis of vesicles isolated from the liquid phase, including cell culture supernatants and blood draws, 2D‐cultured cell assays, or systemic analyses on animal models for biodistribution. Therefore, we have a limited understanding of local EV transfer within tumor tissues. In this review, we discuss the need to study EVs in a physiological tissue context by summarizing the current findings on the impacts of tumor tissue environment on cancer EV properties and transfer and the techniques required for the analysis. Tumor tissue environment is likely to alter EV properties, pose physical barriers, interactions, and interstitial flows for the dynamics, and introduce varieties in the cell types taken up. Utilizing physiological experimental settings and spatial analyses, we need to tackle the remaining questions on physiological EV‐mediated cancer–host cell interactions. Understanding cancer EV‐mediated cellular communications in physiological tumor tissues will lead to developing interaction‐targeting therapies and provide insight into EV‐mediated non‐cancerous cells and interspecies interactions.

中文翻译：

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组织环境对细胞外囊泡介导的癌症-宿主细胞通讯的影响

肿瘤组织密集地充满癌细胞、非癌细胞和 ECM，形成功能结构。癌细胞转移细胞外囊泡（EV），将周围的正常细胞转变为促癌细胞，与其他信号分子和结构成分一起建立有利于肿瘤的环境。这种组织环境在很大程度上影响癌细胞的特性，以及肿瘤组织内 EV 介导的细胞通讯。然而，目前关于 EV 的研究侧重于从液相中分离的囊泡的功能分析，包括细胞培养上清液和抽血、2D 培养细胞测定或对动物模型生物分布的系统分析。因此，我们对肿瘤组织内局部 EV 转移的了解有限。在这篇综述中，我们通过总结当前关于肿瘤组织环境对癌症 EV 特性和转移的影响的研究结果以及分析所需的技术，讨论了在生理组织背景下研究 EV 的必要性。肿瘤组织环境可能会改变 EV 特性，为动力学造成物理障碍、相互作用和间质流动，并引入所吸收的细胞类型的多样性。利用生理实验设置和空间分析，我们需要解决有关生理性 EV 介导的癌症与宿主细胞相互作用的剩余问题。了解生理性肿瘤组织中癌症 EV 介导的细胞通讯将导致开发相互作用靶向疗法，并提供对 EV 介导的非癌细胞和种间相互作用的深入了解。